Nitrosamine

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search

Template:Short description Script error: No such module "Distinguish".

File:Nitrosamine Formulae V.1.svg
Structure of the nitrosamino group

Nitrosamines (or more formally N-nitrosamines) are organic compounds produced by industrial processes.[1]Template:Improve The chemical structure is Template:Chem2, where R is usually an alkyl group.[2] Nitrosamines have a nitroso group (Template:Chem2) that are "probable human carcinogens",[3] bonded to a deprotonated amine. Most nitrosamines are carcinogenic in animals.[4] A 2006 systematic review supports a "positive association between nitrite and nitrosamine intake and gastric cancer, between meat and processed meat intake and gastric cancer and oesophageal cancer, and between preserved fish, vegetable and smoked food intake and gastric cancer, but is not conclusive".[5]

Chemistry

File:Ndma activ.svg
Metabolic activation of the nitrosamine NDMA converts it to the alkylating agent diazomethane[6]

The organic chemistry of nitrosamines is well developed with regard to their syntheses, their structures, and their reactions.[7][8] They usually are produced by the reaction of nitrous acid (Template:Chem2) and secondary amines, although other nitrosyl sources (e.g. Template:Chem, Template:Chem, RONO) have the same effect:[9]

Template:Chem2

The nitrous acid usually arises from protonation of a nitrite. This synthesis method is relevant to the generation of nitrosamines under some biological conditions.Template:Sfn The nitrosation is also reversible, particularly in acidic solutions of nucleophiles.[10] Aryl nitrosamines rearrange to give a para-nitroso aryl amine in the Fischer-Hepp rearrangement.[11]

With regards to structure, the Template:Chem2 core of nitrosamines is planar, as established by X-ray crystallography. The N-N and N-O distances are 132 and 126 pm, respectively in dimethylnitrosamine,[12] one of the simplest members of a large class of N-nitrosamines.

Nitrosamines are not directly carcinogenic. Metabolic activation is required to convert them to the alkylating agents that modify bases in DNA, inducing mutations. The specific alkylating agents vary with the nitrosamine, but all are proposed to feature alkyldiazonium centers.[13][6]

History and occurrence

In 1956, two British scientists, John Barnes and Peter Magee, reported that a simple member of the large class of N-nitrosamines, dimethylnitrosamine, produced liver tumours in rats. Subsequent studies showed that approximately 90% of the 300 nitrosamines tested were carcinogenic in a wide variety of animals.[14]

Tobacco exposure

A common way ordinary consumers are exposed to nitrosamines is through tobacco use and cigarette smoke.[13] Tobacco-specific nitrosamines also can be found in American dip snuff, chewing tobacco, and to a much lesser degree, snus (127.9 ppm for American dip snuff compared to 2.8 ppm in Swedish snuff or snus).[15]

Dietary exposure

Template:Transcluded sectionNitrosamine formation during digestion

Medication impurities

There have been recalls for various medications due to the presence of nitrosamine impurities. There have been recalls for angiotensin II receptor blockers, ranitidine, valsartan, duloxetine, and others.

The US Food and Drug Administration published guidance about the control of nitrosamine impurities in medicines.[16][17] Health Canada published guidance about nitrosamine impurities in medications[18] and a list of established acceptable intake limits of nitrosamine impurities in medications.[19]

Examples

Substance name CAS number Synonyms Molecular formula Physical appearance Carcinogenity category
N-Nitrosonornicotine 16543-55-8 NNN C9H11N3O Light yellow low-melting solid
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone[20] 64091-91-4 NNK, 4′-(nitrosomethylamino)-1-(3-pyridyl)-1-butanone C10H15N3O2 Light yellow oil
N-Nitrosodimethylamine 62-75-9 Dimethylnitrosamine, N,N-dimethylnitrosamine, NDMA, DMN C2H6N2O Yellow liquid EPA-B2; IARC-2A; OSHA carcinogen; TLV-A3
N-Nitrosodiethylamine 55-18-5 Diethylnitrosamide, diethylnitrosamine, N,N-diethylnitrosamine, N-ethyl-N-nitrosoethanamine, diethylnitrosamine, DANA, DENA, DEN, NDEA C4H10N2O Yellow liquid EPA-B2; IARC-2A
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol 76014-81-8 NNAL
N-Nitrosoanabasine 37620-20-5 NAB C10H13N3O Yellow Oil IARC-3
N-Nitrosoanatabine 71267-22-6 NAT C10H11N3O Clear yellow-to-orange oil IARC-3

See also

Additional reading

  • Script error: No such module "Citation/CS1".
  • Script error: No such module "citation/CS1".

References

Template:Reflist

External links

Template:Nitric oxide signaling Template:Portal bar Template:Authority control

  1. ↑ California Water Boards, State Water Resources Control Board, "Nitrosamines", 09 December 2024
  2. ↑ Script error: No such module "Citation/CS1".
  3. ↑ World Health Organization, Medical product alert, Note on Nitrosamine impurities, "Update on Nitrosamine impurities", 20 November 2019
  4. ↑ Script error: No such module "Citation/CS1".
  5. ↑ Script error: No such module "Citation/CS1".
  6. ↑ a b Script error: No such module "Citation/CS1".
  7. ↑ Script error: No such module "citation/CS1".
  8. ↑ Script error: No such module "citation/CS1".
  9. ↑ Template:March6th
  10. ↑ Script error: No such module "citation/CS1".
  11. ↑ Template:March6th
  12. ↑ Script error: No such module "Citation/CS1".
  13. ↑ a b Script error: No such module "Citation/CS1".
  14. ↑ Script error: No such module "citation/CS1".
  15. ↑ Script error: No such module "Citation/CS1".
  16. ↑ Script error: No such module "citation/CS1".
  17. ↑ Script error: No such module "citation/CS1".
  18. ↑ Script error: No such module "citation/CS1".
  19. ↑ Script error: No such module "citation/CS1".
  20. ↑ Hecht, Steven S.; Borukhova, Anna; Carmella, Steven G. "Tobacco specific nitrosamines" Chapter 7; of "Nicotine safety and toxicity" Society for Research on Nicotine and Tobacco; 1998 - 203 pages
Retrieved from "http://debianws.lexgopc.com/wiki143/index.php?title=Nitrosamine&oldid=858259"